{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:58:51Z","timestamp":1792619931667,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T00:00:00Z","timestamp":1679184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007723","name":"Takeda Pharmaceutical Company Limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007723","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The orexin 2 receptor\u2010selective agonist danavorexton (TAK\u2010925) has been shown to produce wake\u2010promoting effects in wild\u2010type mice, narcolepsy\u2010model mice, and individuals with narcolepsy type 1 and type 2. Here, we report wake\u2010promoting effects of danavorexton in non\u2010human primates and healthy men during their sleep phase. Electroencephalogram analyses revealed that subcutaneous administration of danavorexton significantly increased wakefulness in common marmosets (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 at 0.1\u00a0mg\u2005kg<jats:sup>\u22121<\/jats:sup>, and <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 at 1\u00a0mg\u2005kg<jats:sup>\u22121<\/jats:sup> and 10\u00a0mg kg<jats:sup>\u22121<\/jats:sup>) and cynomolgus monkeys (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.05 at 1\u00a0mg\u2005kg<jats:sup>\u22121<\/jats:sup> and 3\u00a0mg\u2005kg<jats:sup>\u22121<\/jats:sup>). In a phase 1b crossover, randomized, double\u2010blind, placebo\u2010controlled and active\u2010controlled study in sleep\u2010deprived healthy participants (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT03522506), modafinil 300\u2009mg (used to demonstrate assay sensitivity) and continuous infusion of danavorexton 44\u2009mg and danavorexton 112\u2009mg showed statistically superior wake\u2010promoting effects to placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a018). Measured using the Maintenance of Wakefulness Test, mean (standard deviation) sleep latencies during infusion of danavorexton 44\u2009mg, danavorexton 112\u2009mg and placebo were 21.4 (8.9), 31.8 (3.2) and 9.2 (6.4) min, respectively. Least\u2010squares mean difference from placebo in average sleep latency was 16.8\u00a0min with danavorexton 44\u2009mg and 30.2\u00a0min with danavorexton 112\u2009mg (both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Karolinska Sleepiness Scale scores were statistically significantly lower (indicating decreased sleepiness) for participants receiving danavorexton than for those receiving placebo during infusion (danavorexton 44\u2009mg, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.010; danavorexton 112\u2009mg, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Together, these results indicate that an orexin 2 receptor agonist increases wakefulness in non\u2010human primates and healthy individuals during their sleep phase.<\/jats:p>","DOI":"10.1111\/jsr.13878","type":"journal-article","created":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T15:48:36Z","timestamp":1679240916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Orexin 2 receptor\u2010selective agonist danavorexton (<scp>TAK<\/scp>\u2010925) promotes wakefulness in non\u2010human primates and healthy individuals"],"prefix":"10.1111","volume":"32","author":[{"given":"Rebecca","family":"Evans","sequence":"first","affiliation":[{"name":"Neuroscience Therapeutic Area Unit Takeda Development Center Americas, Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-3647","authenticated-orcid":false,"given":"Haruhide","family":"Kimura","sequence":"additional","affiliation":[{"name":"Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited  Fujisawa Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited  Fujisawa Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited  Fujisawa Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yukitake","sequence":"additional","affiliation":[{"name":"Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited  Fujisawa Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohisa","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited  Fujisawa Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hazel","sequence":"additional","affiliation":[{"name":"Neuroscience Therapeutic Area Unit Takeda Development Center Americas, Inc.  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